Welcome to the 19th Annual wow, almost 20 years Drug Therapy Decision Making Course An interactive course on common and new drug therapy issues from an evidence based perspective Education should not be the filling of a pail but the lighting of a fire" William Butler Yates
Course Directors Robert Rangno, M.Sc. M.D. Professor Emeritus Faculty of Medicine, UBC James McCormack, B.Sc. (Pharm), Pharm.D. Professor Faculty of Pharmaceutical Sciences, UBC Healthy Skepticism
JM - entire salary comes through the UBC Faculty of Pharmaceutical Sciences - (CREB, PMPRB, legal) BR - retired from UBC - still doing consults Approx 10-15% of our salary is covered by the TI grant from the Ministry of Health We have received no honorarium or research money from the drug industry in the last 18 or so years
2008 Drug Therapy Decision Making Course 15 minute talks 5 minutes questions Conflicts of interest As important as asking questions is to question answers White Marriot pieces of paper Syllabus Challenge the speakers!!!!!! No drug company support Have fun!!!!
Housekeeping Issues Evaluations computer sheets Incentive Booth(s)
Course Directors This Isn t Bob Our role?
Course Directors Where do they come up with these titles?
Issues that drive us crazy
Number Issues
Reuters
Statin meta-analysis - 4.3 years per mmol/l reduction Vascular death (%) Overall mortality (%) Major vascular event (%) No Dia Dia No Dia Dia No Dia No CVD Dia No CVD No Dia CVD Dia CVD Statin 4.2 6.4 7.9 11.0 6.7 9.2 18.5 26.3 No statin 5.3 7.2 9.1 11.9 8.3 11.8 23.5 31.6 Relative risk reduction Absolute risk reduction 18 13 13 9 22 27 21 20 1.1 0.6 1.2 0.9 1.4 2.6 5.0 5.3 Lancet 2008;371:117-25
Treatment of Hypertension in Patients 80 Years of Age or Older Patients 3,845 patients with a SBP > 160 mm Hg, TC 5.3 mmol/l, 12% history of CVD, 60% were female, average age was 83, BMI 25 Treatment Indapamide (1.25 mg) - then indapamide plus perindopril (2 or 4mg) or placebo daily Duration Followed for 1.8 years Results BP differences at the end (15/6 mm Hg lower) - 74% on both drugs N Engl J Med 2008:358
BP elderly results Fatal or nonfatal stroke (%) Serious adverse event (%) Overall mortality (%) MI (%) Any cardiovascular event (%) Placebo 3.6 23.4 12.3 0.5 10 Inda/perin 2.9 18.5 10.1 0.6 7.1 Relative risk reduction 21 18 29 Absolute risk NSS P=0.06 reduction 4.9 2.2 2.9 Number needed to treat 20 45 35 No mention of adverse effects
25,000 patients with vascular disease (75% CAD/ 21% stroke) or diabetes but NO heart failure - either drug or both - 4.5 years no difference in outcome Side effects requiring D/C of drug (R/T/Combo) Hypotensive symptoms (%) - 1.7/2.7/4.8 Cough (%) - 4.1/1.6/4.6 Angioedema (%) - 0.3/0.1/0.2 Diarrhea (%) - 0.1/0.2/0.5
Surrogate Marker Issues
Ezetimibe effect on LDL 1/40 of the dose gives 1/2 the effect Placebo 0.25 mg 1 mg 5 mg 10 mg Clin Ther 2001;23:1209-30
720 patients with familial hypercholesterolemia, avg. age 46, 50% male, BMI 27, 30% smokers 2 years - simvastatin 80 or simvastatin plus ezetimibe 10 mg LDL - mmoles/l - 5 vs 3.7 Mean intima media thickness of carotid artery increased by 0.0058 in S and 0.0111 in S/E - NSS CVD events - n = 7 versus 10 - NSS The definitive trial results? - acute coronary syndrome - are due to be reported in January 2011
Annual Volume of Prescriptions for Ezetimibe and Statins per 100,000 Persons N Engl J Med 2008;358
Denial Issues
Rosuvastatin in older patients with systolic heart failure - CORONA Patients 5,011 heart failure patients (62% Class III) with an LDL 2.9 mmol/l, 60% HX MI, 63% hypertension, 65% were male, 9% were smokers, average age was 73, BMI 27, diabetes 30% Treatment Rosuvastatin 10 mg or placebo daily Duration 3 years Results Cholesterol differences at end of follow-up (mmol/l) Total baseline - 5.4 - (?% lower) LDL baseline - 3.6 - (44% lower) HDL baseline - 1.2 - (5% higher) Triglyc - baseline 2.0 - (21% lower) NEJM 2007;357:2248-61
Rosuvastatin results Death from CV causes, non-fatal MI, non-fatal stroke (%) CV mortality (%) Mortality (%) CV hospitalizations (%) Rosuvastatin 10 mg 27.5 23.1 29.0 43.9 Placebo 29.3 23.7 30.3 46.6 Relative risk reduction Absolute risk reduction Number needed to treat NSS 6 2.7 37 Overall serious adverse events - no difference but # s not reported
Editorialist conclusion enough uncertainty exists about the mechanisms underlying the primary results of the CORONA study that clinicians should continue to prescribe statins for patients with ischemic heart failure and left ventricular systolic dysfunction Frederick A. Masoudi, M.D., M.S.P.H., of the University of Colorado at Denver "This would not deter me from prescribing for a patient with heart failure if the patient otherwise had an indication for statin therapy," Gordon F. Tomaselli, M.D., of Johns Hopkins
The Truth? A Few Good Men
The problem with specialists
No one holds a gun to your head to prescribe/recommend drugs
"EVIDENCE"-BASED PRINCIPLES Evidence Values Individualise Decision-making Evaluation Negligence Common sense Economics
"EVIDENCE"-BASED PRINCIPLES Evidence Seek out evidence from reliable sources and familiarize yourself with the highest level of evidence for the common conditions you treat Values Identify and respect patient values and support their decisions Do not promote fear of a risk promote a sense of wellness Individualise Background risk; the added risk of a "risk factor ; reduction in risk from the therapy (along with the harm risk) Identify specific goals - divided into immediate (symptoms) and theoretic Always use the lowest dose that achieves the goal Decision-making Shared decision making not paternalism
"EVIDENCE"-BASED PRINCIPLES Evaluation Always re-evaluate on a regular basis things change Negligence You get sued for negligence, not thoughtful and well documented shared decision-making It is OK if you don t always follow the guidelines Common sense make it common Economics Use the lowest priced equally effective medication cost is a side effect Only order tests if the results will change what you would do and make sure the patients understands
Life is a Matter of Balance
Just Do The Right Thing
If Nothing Works
Course Directors JAMESThe sun did not shine. BOB It was too wet to play. JAMES So we sat in your house BOB All that cold, cold, wet day JAMES I sat there with Robert. BOB We sat there, we two. JAMES And I said "How I wish We had something to do!" BOBAnd then Something went click! JAMES And with that click came a shtick BOB We said! Let s use a Seuss theme, now that will be fun JAMES Everybody will like it except for thathcycone BOB We ll give people titles, we ll give them no choice JAMES They ll have to use them or we ll give them no voice BOBSo we hope you ll have fun and perhaps learn something swell JAMES And if not you can really all just go to the course next year and try again